For patients maintained on artificial mechanical ventilation, a primary concern of the clinician is the mechanical status of the lungs, which can often be inferred from estimates of total respiratory or pulmonary resistance (R) and elastance (E). Several techniques exist to assess R and E during mechanical ventilation at a given frequency, tidal volume, or mean airway pressure. Bates, J. H. T., and A. M. Lauzon, xe2x80x9cA nonstatistical approach to estimating confidence intervals about model parameters: application to respiratory mechanicsxe2x80x9d, IEES Trans. Biomed. Eng. 39: 94-100, 1992; Kaczka, D. W., G. M. Barnas, B. Suki, and K. R. Lutchen, xe2x80x9cAssessment of time-domain analyses for estimation of low-frequency respiratory mechanical properties and impedance spectraxe2x80x9d, Ann. Biomed. Eng. 23: 135-151, 1995; Lutchen, K. R., D. W. Kaczka, B. Suki, G. Bamas, G. Cevenini, and P. Barbini, xe2x80x9cLow-frequency respiratory mechanics using ventilator-driven forced oscillationsxe2x80x9d; J. Appl. Physiol. 75: 2549-2560, 1993; and Peslin, R., J. Felico de Silva, F. Chabot, and C. Duvivier, xe2x80x9cRespiratory mechanics studied by multiple linear regression in unsedated ventilated patientsxe2x80x9d, Eur. Respir. J. 5: 871-878, 1992.
Such estimates, however, do not permit inference on the level or distribution of obstruction in the airways, or the relative stiffness or viscance of the lung or respiratory tissues. Recent studies have suggested that the frequency dependence of R and E in breathing rates from 0.1 to 8 Hz embodies information needed to partition airway and tissue mechanical properties, or establish the dominant pattern of constriction in the airway tree. Petak, F., Z. Hantos, A. Adamicza, and B. Daroczy, xe2x80x9cPartitioning of pulmonary impedance: modeling vs. alveolar capsule approachxe2x80x9d, J. Appl. Physiol. 75: 513-521, 1993; Lutchen, K. R., and H. Gillis, xe2x80x9cRelationship between heterogeneous changes in airway morphometry and lung resistance and elastancexe2x80x9d, J. Appl. Physiol. 83: 1192-1201, 1997.
The frequency dependence of R and E can be derived from input impedance (Z), the complex ratio of pressure to flow during external forcing as a function of frequency. It is difficult to measure Z at low frequencies in ventilator-dependent patients, especially those with chronic obstructive pulmonary disease (COPD). Measurements relying on small-amplitude forced oscillations generated by loud-speakers require that the patient be disconnected from ventilatory support, which becomes impractical if low frequency information is desired, and becomes dangerous in patients with COPD. Navajas, D., R. Farre, J. Canet, M. Rotger, and J. Sanchis, xe2x80x9cRespiratory input impedance in anesthetized paralyzed patientsxe2x80x9d, J. Appl. Physiol. 69 1372-1379, 1990. Other investigators have used spectral analysis on standard volume-cycled ventilator waveforms to extract impedance information without disrupting mechanical ventilation (see Barnas, G. M., P. Harinath, M. D. Green, B. Suki, D. W. Kaczka, and K. R. Lutchen, xe2x80x9cInfluence of waveform and analysis technique on lung and chest wall propertiesxe2x80x9d, Respir. Physiol. 96: 331-344, 1994), but these attempts have been unsuccessful due to the waveforms"" poor signal-to-noise ratio at harmonics above the frequency of ventilation as well as nonlinear harmonic distortion of the resulting pressure signal. Suki, B., and K. R. Lutchen, xe2x80x9cPseudorandom signals to estimate apparent transfer and coherence functions of nonlinear systems: applications to respiratory mechanicsxe2x80x9d, IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992 Recent studies have demonstrated that a broad-band Optimal Ventilator Waveform (OVW) can be used to measure Z in awake subjects with mild-to-moderate obstruction during tidal-like excursions with minimal harmonic distortion. Kaczka, D. W., E. P. Ingenito, B. Suki, and K. R. Lutchen, xe2x80x9cPartitioning airway and lung tissue resistances in humans: effects of bronchoconstrictionxe2x80x9d, J. Appl. Physiol. 82: 1531-1541, 1997; Lutchen, K. R., K. Yang, D. W. Kaczka, and B. Suki, xe2x80x9cOptimal ventilation waveforms for estimating low-frequency respiratory impedancexe2x80x9d, J. Appl. Physiol. 75: 478-488, 1993. However the original OVW is oscillatory, which presents two problems. First, the active expiratory component of the OVW makes it impossible to use in patients whose obstruction may be so severe that their airways can be dynamically compressed during expiration. Mead, J., I. Lindgren, and E. A. Gaensler, xe2x80x9cThe mechanical properties of the lungs in emphysemaxe2x80x9d, J. Clin. Invest. 34: 1005-1016, 1955. Second, it is generated via a closed system in which no fresh gas is delivered to the patient, and therefore long-term ventilation is impossible.
Besides the experimental limitations of measuring Z, an additional problem arises in its physical interpretation in patients with COPD. Regardless of the methods used to generate or acquire the data, Z has been computed using traditional spectral methods, which assume system linearity and time invariance. Daroczy, B., and Z. Hantos, xe2x80x9cAn improved forced oscillatory estimation of respiratory impedancexe2x80x9d, Int. J. Bio.-Med. Comput. 13: 221-235, 1982; Michaelson, E. D., E. D. Grassman, and W. Peters, xe2x80x9cPulmonary mechanics by spectral analysis of forced random noisexe2x80x9d, J. Clin. Invest. 56: 1210-1230, 1975. Depending on the patient""s pathology, such assumptions can be grossly invalid. For example, the phenomena of dynamic airway compression and expiratory flow limitation are highly nonlinear processes, in which flow is no longer determined by the pressure drop across the airways. Fry, D. L., R. V. Ebert, W. W. Stead, and C. C. Brown, xe2x80x9cThe mechanics of pulmonary ventilation in normal subjects and in patients with emphysemaxe2x80x9d, American Journal of Medicine 16: 80-97, 1954. In general, linear approximations in patients with severe obstruction must be restricted to data in which such processes are known to be absent, such as inspiration.
Current mechanical ventilators are operable in passive or active modes. With active modes, an effort by the patient triggers the delivery of a breath. With passive modes, only the ventilator is active and it delivers the breath at a pre-set breathing rate (frequency), volume per breath (tidal volume (VT)) and waveform. The most common active mode is referred to as volume support. With volume support, a pre-set flow wave shape is delivered via a ventilator pressure source during inspiration. Ventilator controlled solenoid valves then enable the patient to passively expire to the atmosphere. Current volume support waveforms include a) a step to a constant flow rate (i.e. step waveform) delivered to produce the desired VT within the inspiratory time (TI); b) a ramp in which a peak flow is delivered immediately in the inspiration followed by a linear decrease in flow for the remainder of TI; and c) a sinusoid in which peak flow is reached proximal to the middle of inspiration.
The primary goal of all waveforms is to maintain blood gas levels (O2 and CO2) to sustain normoxia and nomocapnia. Because ventilation via pressure produced at the mouth is not natural, another requirement is that the ventilator not produce excessive pressure at the airway opening. This can lead to barotrauma (intralung airway damage), which in turn can cause respiratory distress.
During mechanical ventilation, the clinician is concerned (among other things) with the mechanical status of the patient. Specifically, it is desirable to estimate the degree of airway obstruction or constriction, the distribution of constriction in the airways, and the relative stiffness and viscosity of the lung tissues. This assessment can be made by examining the resistance R and elastance E at several frequencies surrounding normal breathing rates (i.e., from about 0.1-8 Hz). The behavior of the R and E spectra over this frequency range are very distinct for particular forms and degrees of lung disease. Such information is helpful in a) determining the severity of any lung disease that is present and its response to therapy and the mechanical ventilation itself; b) the pressures necessary at the airway opening to deliver a desired volume; and c) determining the likelihood of success in weaning the patient from the ventilator.
Current mechanical ventilation waveforms permit assessment of lung mechanical properties at only a single breathing rate, that of the ventilator itself. Knowledge of R and E at this particular frequency may be very misleading as to the mean level of airway resistance and the relative distribution of the disease among the airways and between the airways and tissues. Likewise, the waveform shapes available for volume ventilation are very limited and not optimized for a) minimizing airway pressures or b) maximizing ventilation distribution.
The present invention is directed to an apparatus and method that provides a novel ventilator waveform having an enhanced inspiratory flow pattern ideally suited for determining an effective xe2x80x9cinspiratory impedancexe2x80x9d in ventilator-dependent patients, and/or patients with severe obstruction resulting in expiratory flow-limitation. This waveform is referred to herein as the xe2x80x9cEnhanced Ventilator Waveformxe2x80x9d (EVW). In theory, the EVW will maintain ventilatory support while simultaneously providing an accurate and sensible assessment of the mechanical status of the lungs or total respiratory system. A technique for computing inspiratory impedance, for example a weighted-least-squares technique, is also provided.
The EVW technique of the present invention ensures that normal (tidal) volume levels are delivered during each inspiration, and that expiration remains passive. Furthermore, accurate estimation of lung resistance and elastance is established for several frequencies surrounding the primary ventilator breathing rate. From the resistance and elastance data, the mean level and structural distribution of airway versus tissue constriction conditions in the lung can be inferred. Additionally, the distribution of delivered gas is more uniform (i.e, more beneficial to the patient) with the EVW, as compared to conventional waveforms.
In a first embodiment, the method of the present invention is directed to a method for estimating the frequency dependence of respiratory impedance in a patient. A ventilation function is generated comprising an inspiratory waveform formed by a plurality of energy waves at predetermined frequencies. Flow and pressure data are estimated during delivery of the ventilation function to the patent. Flow and pressure waveforms are generated from the estimated flow and pressure data. Frequency components in the flow and pressure waveforms are calculated at each predetermined frequency. A respiratory impedance estimate is calculated at each predetermined frequency based on the flow and pressure waveforms.
In a preferred embodiment, the respiratory impedance estimate includes estimates of resistance and elastance components. Estimation of the flow and pressure data preferably comprises measuring pressure and flow data at the delivery apparatus delivering the ventilation function, or optionally, may comprise measuring pressure and flow data at the input to the respiratory system. The frequency components of the flow and pressure waveforms may comprise amplitude and phase.
In a preferred embodiment, the frequency components in the flow and pressure waveforms are calculated at each predetermined frequency using time-weighted linear regression, with calculations being performed in the time domain, and wherein the flow and pressure waveforms are time-domain waveforms. Each time-domain flow and pressure waveform may comprise a sum of sine waves of the predetermined frequencies.
The respiratory impedance estimate may be based on an impedance calculation at each predetermined frequency as a ratio of the pressure and flow waveforms. The frequencies may be selected according to no-sum-no-difference criteria. The energy waves may have magnitudes that are chosen to ensure sufficient signal-to-noise in the resulting estimate, and may have phases that are chosen such that the resulting ventilation function delivers sufficient fluid volume to maintain ventilation.
In a preferred embodiment the patient is isolated from the ventilation function to allow for natural expiration, with data being collected only during inspiration. Accordingly, the system may be configured to permit different inspiration and expiration time durations.
The predetermined frequencies are preferably within a range of 0.1 Hz and 8 Hz. High-frequency components may be applied to the ventilation function to provide for a therapeutic effect.